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Abstract. Oncogene-induced senescence (OIS) may be a response to oncogenic activation, acting as a natural barrier against carcinogenesis at a premalignant stage. Thus, numerous cells in premalignant lesions enter senescence, but none or few in malignant tumours. This event could be due to the loss of senescence pathway effectors, including p16 (INK4a)-pRb or ARF-p53. The aim of this study was to characterize and compare the expression of certain senescent markers between oral precancer and cancer tissue samples. The expression of cyclin D1, Rb, maspin, p53 and mouse double minute 2 (MDM2) was analyzed in 20 paraffin-embedded tissue samples of normal oral mucosa (NOM), 14 samples of oral leukoplakia without dysplasia (OLD-), 11 samples of leukoplakia with dysplasia (OLD+) and 15 samples of oral squamous cell carcinoma (OSCC) by immunohistochemistry in tissue arrays. The expression of p16-pRb pathway markers, cyclin D1, maspin and Rb, was more frequent in OLD+ samples than in OSCC samples, although a statistical significance was only observed for maspin (P=0.036). Cyclin D1 expression was also significantly more frequent in OLD-samples vs. NOM samples. For the ARF-p53 pathway, the expression of p53 and MDM2 was significantly more frequent in the OLD-samples compared to in the NOM ones. These findings may indicate a role for cellular senescence in oral carcinogenesis, considering maspin as a reliable senescence marker and prognostic factor in oral premalignant lesions.

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We studied 44 cases of small cell bladder carcinoma (SCBC) and 2 cases of large cell neuroendocrine bladder carcinoma (LCNBC) to determine the immunohistochemical profile and biologic behavior. Thyroid transcription factor (TTF)-1, cytokeratin (CK)20, chromogranin A (CgA), synaptophysin, neuron-specific enolase (NSE), and Leu-7 studies were performed. TTF-1+ cases were stained for surfactant protein A (SP-A). The immunohistochemical profile for 44 SCBC cases was as follows: TTF-1+, 11 (25%); CK20+, 3 (7%); CgA+, 13 (30%); synaptophysin+, 22 (50%); NSE+, 35 (80%); and Leu-7+, 30 (68%), and for 2 LCNBC cases was as follows: TTF-1+, 2 (100%); CgA+, (50%); synaptophysin+, 1 (50%); NSE+, 2 (100%); and Leu- 7+, 2 (100%). All cases with TTF-1 expression were negative for SP-A, except 1 case. This case was a mixed SCBC with TTF-1 expression in the urothelial component, which also expressed SP-A. Immunohistochemical markers were not associated with survival. The prognosis of SCBC is relatively better than its pulmonary counterpart. LCNBC seems to be a rarely recognized entity. TTF-1 expression is not limited to small cell lung carcinoma.

The cellular proteome shows a dynamic profile and is subjected to changes in response to various stimuli and disease progression. Lung cancer remains the leading cause of cancer death in industrialized countries. In an attempt to find new disease markers, patients suffering from lung carcinoma have been selected to achieve differential protein expression patterns between normal and neoplasic tissue. After two-dimensional electrophoresis, the spots of interest were digested and identified by matrix-assisted laser desorption/ionization (MALDI) peptide mass fingerprinting. This information will provide a more comprehensive understanding of the disease progression and might constitute a method to complement histopathological diagnosis.

BackgroundHuman Papillomavirus (HPV) genotype distribution and co-infection occurrence was studied in cervical specimens from the city of Madrid (Spain), as a contribution to the knowledge of Human Papillomavirus genotype distribution and prevalence of carcinogenic HPV types in cervical lesions in Spain.MethodsA total of 533 abnormal specimens, from the Hospital General Universitario “Gregorio Marañón” of Madrid, were studied. These included 19 benign lesions, 349 cervical intraepithelial neoplasias 1 (CIN1), 158 CIN2-3 and 7 invasive cervical carcinomas (ICC). HPV genotyping was performed using PCR and tube array hybridization.ResultsWe detected 20 different HPV types: 13 carcinogenic high-risk HPV types (HR-HPVs), 2 probably carcinogenic high-risk HPV types (PHR-HPVs) and 5 carcinogenic low-risk HPV types (LR-HPVs). The most frequent HPV genotypes found in all specimens were HPV16 (26.0%), 31 (10.7%) and 58 (8.0%). HPV 18 was only detected in 5.0%. Co-infections were found in 30.7% of CIN 1 and 18.4% cases of CIN2-3. The highest percentage of HR HPVs was found in those specimens with a CIN2-3 lesion (93.7%).ConclusionAs our study shows the current tetravalent vaccine could be effective in our geographical area for preventing all the invasive cervical carcinomas. In addition, upon the estimates of the important presence of other HR-HPV types – such as 31, 58, 33 and 52 – in different preneoplasic lesions the effectiveness of HPV vaccination in our geographical area, and others with similar genotype distribution, should be limited.

To our knowledge our study suggests for the first time in the literature a positive effect of sildenafil in the immediate posttransplantation outcome of warm ischemic kidneys without secondary systemic effects.

Non-small cell lung cancer (NSCLC) is a major public health problem, accounting for more cancer-related deaths than any other cancer. Both immunotherapy, based on the expression of tumor-specific antigens, and targeted therapy, based on the presence of oncogenic mutations, are under development for NSCLC. In this study, we analyzed the expression of MAGE-A, a cancer-testis antigen, in tumors from a cohort of patients with resected NSCLC with respect to their clinicopathologic characteristics and their mutational status for the EGFR and KRAS genes. We found MAGE-A expression by IHC in 43% of the tumors. MAGE-A expression was significantly more frequent in squamous tumors than in adenocarcinomas, did not correlate with disease stage, but was correlated significantly with high tumor grade and worse survival. EGFR and KRAS mutations were present in adenocarcinomas, but not in squamous tumors. Whereas the presence of EGFR mutations did not seem to affect survival, the presence of KRAS mutations was associated with early-stage disease and better survival. MAGE-A expression was absent from adenocarcinomas with KRAS mutations, but not significantly different in tumors with or without EGFR mutations. Together, the reported results provide guidance for the design of combination therapies in patients with NSCLC. Cancer Immunol Res; 2(10); 943-8. Ó2014 AACR.